NEW YORK (Reuters Health) – Children taking the drug Gleevec for a rare form of childhood leukemia may show a slow-down in their growth -- at least if they start the drug before puberty, a new study suggests.
The findings, published in the Journal of Pediatrics, confirm past reports of impaired growth in some children on Gleevec, which is used to treat chronic myelogenous leukemia, or CML.
But they also suggest that the effects are seen only in children who have not yet reached puberty -- and that some kids might experience "catch-up" growth once they do hit puberty.
CML is a cancer that starts in the blood-forming cells of the bone marrow. In the U.S., it is diagnosed in about 4,600 people each year, most often older adults. CML only rarely affects children, who account for about 2 to 4 percent of cases.
The drug Gleevec, known generically as imatinib, has become the first-choice CML treatment since it arrived on the scene in 2001. The drug does not cure the cancer, but it inhibits a specific protein that allows CML to grow and spread. People with the cancer take the drug indefinitely to prevent its progression.
The potential effects of Gleevec on children's growth are not going to change its status as the treatment of choice for CML, according to Dr. Sonali Smith, an associate professor at the University of Chicago who was not involved in the study.
"It's the standard of care for CML in children and adults," said Smith, who is a member of the American Society of Clinical Oncology's communications committee and a lymphoma researcher.
But, she told Reuters Health, "parents should at least be advised that their children may have a delay in growth, and that there's a chance that they'll have catch-up growth during puberty."
The drug's manufacturer, Novartis, added the potential effects on children's growth to the product's prescribing information in 2010.
Because Gleevec has only been around for a relatively short time, and CML is rare in children, there is not much information on the drug's potential long-term side effects in kids.
It will be important for studies to continue to follow young people on the drug, Smith said.
In the current study, researchers led by Dr. Haruko Shima, of Keio University in Tokyo, looked at the medical records of 48 children with CML. All had started Gleevec as a first-line therapy sometime between 2001 and 2006.
A majority of the children showed some amount of growth deceleration after starting Gleevec.
The researchers measured the kids' heights before starting Gleevec, and every year thereafter. Then they calculated how far, if at all, each child deviated from age- and sex-adjusted norms.
In general, a height more than 2 "standard deviations" below the norm would be considered stunted growth, according to the World Health Organization.
Of the children taking Gleevec, just over half were more than 0.5 standard deviations below the average for their age and sex, including one-third who were behind by more than 1 standard deviation.
When the researchers took a closer look, they found that the height effect seemed to be largely limited to the 27 children who started Gleevec before puberty.
And there were some signs that once those children went through puberty, the growth effects faded. Of eight children the researchers were able to follow to older ages, four showed "catch-up" growth during puberty, despite still being on Gleevec.
That finding, according to Smith, offers "some reassurance" -- though, she noted, it is based on a small number of children, and still means that half of the kids did not have catch-up growth.
Why Gleevec might hinder younger kids' growth is not clear, but one possibility is that it affects the bones' growth plates, according to Shima's team.
During puberty, when growth depends largely on sex hormones, the drug may have little impact, the researchers say.
There are two newer drugs in the same class as Gleevec, known as tyrosine kinase inhibitors because they target specific enzymes in CML cells that allow the cancer to grow.
Those two medications, dasatinib (Sprycel) and nilotinib (Tasigna), are more potent than their older cousin and have for several years been used for patients whose cancer stops responding to Gleevec. They were just recently approved as first-line treatments.
It's not yet known whether the newer drugs have different long-term side effects, including effects on children's growth, Smith said.
Novartis did not respond to requests for comment.
SOURCE: http://bit.ly/jgSaiI Journal of Pediatrics, online May 18, 2011.
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